SCREENING FOR EA EARL RLY Y LUN UNG G CANC ANCER ER Pang Yong Kek
Lecture Outline ■ Why performing screening? ■ How to improve early detection? ■ Benefits and Risks of screening ■ Challenges in screening ■ Conclusion
Why Performing Screening? ■ Lung cancer is one of the commonest cancer afflicting mankind ■ Vast majority of the victims have advanced disease at the time of presentation ■ Despite the significant improvement made in treatment modality, mortality of lung cancer remains high – In 2018, it is estimated that 154,050 deaths from lung cancer will occur in the United States. – Five-year survival rates for lung cancer are only 18%
Lung cancer In Malaysia, lung cancer accounts for • 13.8% of all cancers in males and • 3.8% of all cancers in females Second Report of the National Cancer Registry. Cancer incidence in Malaysia, 2003. National Cancer Registry, Malaysia (http:www.acrm.org.my/ncr)
Clinical stage of NSCLC at diagnosis - UMMC Stage 3b & 4 = 69% n = 580 (37%) (32%) No of patients Stage 3a, 7% Stage of disease 76% of patients with NSCLC present with stage III or stage IV disease 1. Liam CK et al . Respirology 2000; 5:355-61; 2. Liam CK et al . Chest 2002; 121:309-10
Why Performing Screening? ■ Screening often leads to detection of early stage disease ■ Early stage disease = Higher chance curative treatment = Better Life Expectancy + Improved Quality of Life
How To Screen? ■ Most of the early lung cancer does not have any sign or symptom, ■ Imagi ging g of the chest t has been regarded as a potentially useful tool to identify the nodule in the lung ■ Historical study: CXR R & sputum utum cytology logy versus standard of care has failed to demonstrate survival benefit in high risk individuals 1. Moyer VA, Force USPST. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2014;160:330 – 338. 2. Detterbeck FC, Mazzone PJ, Naidich DP, Bach PB. Screening for lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143:e78S – 92S.
How To Screen? ■ In recent years, due to advances made in imaging technology, the idea has been re-investigated using low-dose CT scan (LDCT) Source: The Valley Health Cancer Center website
NLST Study ■ The National Lung Screening Trial (NLST) is a trial conducted on over 53,000 high-risk individuals in the US. ■ They are defined as – Aged 55 – 74 years – Current smokers or – Ex-smokers (who had quit ≤ 15 years) – 30 pack-years
NLST Study ■ Subjects were randomised for screening with LDCT Thorax versus Chest X-ray ■ Each subject will get ≥ 3 scans ( baseline and annually for 2 years ) ■ After that they were followed up for another 3.5 years Result: ■ the LDCT arm showed a 20% (95% CI, 6.8 – 26.7; P=.004) reduction in mortality from lung cancer compared to the CXR
Tobacco and Risk of Lung Cancer ■ The overall relative risk (RR) for lung cancer is ≈ 20-fold higher for smokers than for non-smokers. ■ In general, the more tobacco is smoked, the higher is the risk ■ Cessation of tobacco smoking decreases the risk for lung cancer.
Other Risk Factors of Lung Cancer ■ Although smoking tobacco is a well-established risk factor for lung cancer, other environmental and genetic factors also increase the risk These include: ■ Occupational exposure ■ History of lung or other cancers ■ Family history of cancer
Other Risk Factors - Occupational exposure Carcinogens targeting the lungs include ■ arsenic, chromium, asbestos, nickel, cadmium, beryllium, silica, diesel fumes, coal smoke, and soot. Radon exposure
Other Risk Factors – Previous cancer ■ Patients with other cancers are also at increased risk of cancer, e.g. : – Survivors of primary lung cancer, lymphomas, cancers of the head and neck, or smoking-related cancers, such as bladder cancer. ■ Patients previously treated with chest irradiation have a 13 13-fold ld increased risk of developing a new primary lung cancer, ■ Those who have previously been treated with alkylating agents (chemotherapy) have an estimated RR of 9.4
Other Risk Factors - Family history of cancer ■ Several studies have shown the 1st degree relatives of a lung cancer patient are at increased risk of lung cancer ■ A meta-analysis of 28 case-control studies and 17 observational cohort studies showed an RR of 1. 1.8 (95% CI, 1.6 – 2.0) for individuals with a sibling/parents or a first-degree relative with lung cancer ■ The risk is greater in individuals with multi ltiple ple affected ed family ily members mbers or who had a cancer diagnosis at a young g age.
Selection of individuals for Screening ■ The NCCN Panel recommends that only those with high risk sk should be screened ■ Those with moderate or low risk should not be screened ■ In addition, only those who are the poten enti tial al candid idat ates es for curati ative therap rapy should be screened.
High Risk Patients ■ Group 1: – Individuals aged 55 to 74 years with a ≥ 30 pack-year history of smoking tobacco who currently smoke or, if former smoker, have quit within 15 years (category 1). ■ Group 2 – Individuals aged 50 y years or older der with a ≥ 20 pack -year history of smoking tobacco and with th one e addi ditional tional risk k factor or (category 2A). (Screening beyond the NLST criteria)
High Risk Patients For Group 2, screening may be offered if they have one of the additional risk factors below: ■ personal history of cancer or lung disease, ■ family history of lung cancer, ■ radon exposure, ■ occupational exposure to carcinogens.
Benefits ■ Detection of early disease when it is still curable – Although patients with earliest-stage disease (IA) may have a 5-year survival rate of ≈ 75% with surgery, the outcomes quickly decrease with increasing stages – In the NLST, 356 participants died of lung cancer in the LDCT arm and 443 participants died of lung cancer in the chest radiograph arm. – To prevent 1 death from lung cancer, 320 individuals with high-risk factors must be screened with LDCT.
Benefits ■ Improved survival
Benefits ■ Improved quality of life – as a result of – Early disease detection and curative treatment ■ The NLST found that 40% of the cancers detected in the CT-screening group were stage IA, 12% were stage IIIB, and 22% were stage IV. ■ Conversely, 21% of the cancers detected in the CXR group were stage IA, 13% were stage IIIB, and 36% were stage IV. ■ These results suggest that LDCT screening decreases the number of cases of advanced National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395 – 409.
Benefits ■ Identification of other treatable disease, e.g. COPD, coronary artery disease National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395 – 409.
Benefits ■ Long-term cost may be reduced – Upfront costs, e.g. screening, additional diagnostic procedures and other interventions will increase; however – Future costs of treating advanced diseases with chemotherapy, targetable agents, immunotherapy, radiation therapy and others will be reduced
Benefits ■ Provide an opportunity to persuade chronic smokers to stop smoking
Risks/Harms ■ Screening leads to identification of many false positive nodules, which result in many unnecessary interventions – In the NLST, the false-positive rate was 96.4% for the CT screening group. – This is reduced to 33% with 2 annual sequential LDCT. – Those who were screened positive may require interval imaging, percutaneous needle biopsy, or even surgical biopsy
Risks/Harms ■ Some of these procedures are not without any risk – the average surgical mortality rate for major lung surgery across the US is 5% 5%, and the frequency of serious complications is > > 20%.
Risks/Harms ■ False-negative results – may delay or prevent diagnosis and treatment because of a false sense of good health
Risks/Harms ■ Futile detection of small aggressive tumour ■ Futile detection of indolent disease ( over-diagnosis )
Risks/Harms ■ Identification of any nodule will lead to anxie iety ty for the screened subjects ■ False se-posi positiv tive and indeterm erminat inate results sults may decrease quality of life because of mental tal anguish uish and additio tional nal testin sting
Risks/Harms ■ Risk sk of radiat iation ion ■ Using low-dose techniques, the mean effective radiation dose is 1.5 mSv (SD ± 0.5 mSv) compared with an average of 7 mSv for conventional CT scan ■ The radiation dose of LDCT is 10 X X that of CXR ■ Brenner et al estimated a 1.8% increase in lung cancer cases if 50% of all current and former smokers in the US between 50 and 75 years of age were to undergo annual screening LDCT.
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